Pyramidal and granule cells (Fig. 5.1A & B)

Pyramidal cells have large, pyramid-shaped cell bodies that range from 20–120 µm in diameter. They are excitatory neurons that have numerous apical and basal dendrites and a single axon that projects out of the cortex. Pyramidal cells are particularly prominent in motor and premotor areas. Granule cells (or stellate cells) are star-shaped multipolar neurons that have short axons and make local synaptic contacts, tending to be enriched in sensory cortices. They are much smaller than pyramidal cells, with a typical diameter of less than 20 µm, and may be excitatory or inhibitory. The cerebellar cortex also contains two main types of nerve cell: granule cells (similar to those in the cerebral cortex) and Purkinje cells (large efferent neurons, equivalent to cortical pyramidal cells; see Fig. 5.1C).

Cortical lamination

More than 90% of the cerebral cortex has a characteristic six-layered structure that appeared with the evolution of the mammalian brain (Fig. 5.2). For this reason it is referred to as neocortex (Greek: neos, new). Although the same six layers can be identified in all neocortical regions at some stage of development, they are not always present in the mature brain. For instance, the motor and premotor areas of the frontal neocortex are referred to as agranular cortex since they have lost their internal granule cell layer.

Different types of cortex

The cerebral cortex can be divided into more than fifty Brodmann areas based on subtle differences in the cortical structure (referred to as cytoarchitectonics) but there are three major cortical types (Fig. 5.3):

The majority of the ‘non-neocortical’ regions belong to the limbic lobe and are primarily concerned with emotion, memory and olfaction (the sense of smell). The term paralimbic cortex is used to describe non-neocortical regions outside of the limbic lobe proper, including the posterior orbital cortex, anterior insula and temporal pole.

Dendritic spines

The dendrites of many neurons are studded with thousands of tiny, mushroom-shaped dendritic spines (Fig. 5.4). These include the medium spiny neurons that make up 95% of cells in the basal ganglia. In the cerebral cortex, all pyramidal cells have dendritic spines, whereas stellate cells may be spiny or smooth. Each dendritic spine is the site of an incoming excitatory synapse and a typical cortical pyramidal neuron has more than 10,000 spines. They are dynamic structures that can form, change shape or disappear altogether and are thought to be important in synaptic plasticity (Greek: plastikos, able to be moulded) and learning. Long-term memories may be mediated by the growth of new spines or the strengthening and enlargement of existing ones.

Subcellular organelles

The neuronal cell body or soma (Greek: soma, body) contains the same organelles found in other cell types (Fig. 5.5) but the machinery for protein synthesis and gene transcription is particularly prominent (Fig. 5.6A). The perinuclear cytoplasm or perikaryon (Greek: peri, around; cyton, kernel) contains a well-developed network of rough endoplasmic reticulum, often arranged in clumps called Nissl bodies. The Golgi apparatus is also prominent and is the site of post-translational modification and sorting of proteins including ion channels, neurotransmitter receptors and membrane ion pumps.

Lipofuscin and neuromelanin

Neurons have a high rate of membrane turnover and gradually accumulate non-digestible membrane components within lysosomal residual bodies. These contain golden-brown material called lipofuscin (pronounced: lipo-FUSKIN). This so-called ‘age pigment’ accumulates over time as a by-product of membrane turnover and is also abundant in the heart and liver. Catecholamine-synthesizing neurons contain the dark brown pigment neuromelanin (Fig. 5.6B); these include the substantia nigra of the midbrain and the locus coeruleus of the pons (see Ch. 1).

Vesicles

Neurons contain various types of membrane-bound vesicle. Neurotransmitters and neuropeptides are stored in the axon terminal (prior to release) within synaptic vesicles (see Ch. 7). Coated vesicles are derived from internalization of membrane constituents and macromolecules that have been taken up from the extracellular fluid by receptor-mediated endocytosis.

Microtubules

Microtubules are tubular polymeric proteins that are composed of repeating subunits of alpha and beta tubulin. They are 24 nm in diameter and up to 1 mm in length. Some microtubules are stable, whereas others are dynamic and can grow or shrink by the addition or removal of tubulin subunits. Microtubules are polarized. The part that is closest to the neuronal cell body is arbitrarily termed the minus (–) end and that which is nearer to the axon terminal is designated the plus (+) end. Microtubules are stabilized by binding to a range of microtubule associated proteins (MAPs). These include the phosphoprotein tau which accumulates in various degenerative conditions including Alzheimer’s disease (Ch. 12).

Neurofilaments

Neurofilaments are twisted protein strands of approximately 10 nm diameter and variable length. They are part of the large family of intermediate filaments. There are three neurofilament subunits or chains that differ in molecular weight: light (NF-L), medium (NF-M) and heavy (NF-H). These subunits form dimers, each with the NF-L subunit. After dimerisation they assemble in pairs to form biochemically stable tetramers. Neurofilaments have negatively charged side-arms that limit their packing density and are arranged at right angles to the long axis of the axon, helping to determine its calibre.

Microfilaments

The neuron also contains a network of microfilaments that is particularly well-developed immediately beneath the plasma membrane as the cortical cytoskeleton. Microfilaments are a family of double-stranded fibrillar proteins that are around 5–7 nm in diameter and up to 800 nm in length. One of the most important members is the contractile protein actin. The cortical cytoskeleton interacts with membrane-associated and integral membrane proteins (e.g. receptors and ion channels) and helps to create localized ‘domains’ within the plasma membrane. In addition, the cortical cytoskeleton is anchored to the extracellular matrix via transmembrane linkage proteins.